title: Impact of HDL genetic risk scores on coronary artery calcified plaque and mortality in individuals with type 2 diabetes from the Diabetes Heart Study.
abstract: BACKGROUND
  Patients with type 2 diabetes (T2D) are at elevated risk for cardiovascular disease (CVD) events and mortality. Recent studies have assessed the impact of genetic variants affecting high-density lipoprotein cholesterol (HDL) concentrations on CVD risk in the general population. This study examined the utility of HDL-associated single nucleotide polymorphisms (SNPs) for CVD risk prediction in European Americans with T2D enrolled in the Diabetes Heart Study (DHS).
  
  
  METHODS
  Genetic risk scores (GRS) of HDL-associated SNPs were constructed and evaluated for potential associations with mortality and with coronary artery calcified atherosclerotic plaque (CAC), a measure of subclinical CVD strongly associated with CVD events and mortality. Two sets of SNPs were used to construct GRS; while all SNPs were selected primarily for their impacts on HDL, one set of SNPs had pleiotropic effects on other lipid parameters, while the other set lacked effects on low-density lipoprotein cholesterol (LDL) or triglyceride concentrations.
  
  
  RESULTS
  The GRS were specifically associated with HDL concentrations (4.90 × 10(-7) < p < 0.02) in models adjusted for age, sex, and body mass index (BMI), but were not associated with LDL or triglycerides. Cox proportional hazards regression analysis suggested the HDL-associated GRS had no impact on risk of CVD-mortality (0.48 < p < 0.99) in models adjusted for other known CVD risk factors. However, associations between several of the GRS and CAC were observed (3.85 × 10(-4) < p < 0.03) in models adjusted for other known CVD risk factors.
  
  
  CONCLUSIONS
  The GRS analyzed in this study provide a tool for assessment of HDL-associated SNPs and their impact on CVD risk in T2D. The observed associations between several of the GRS and CAC suggest a potential role for HDL-associated SNPs on subclinical CVD risk in patients with T2D.
authors.affiliation: Molecular Genetics and Genomics Program, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Raffield
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Cox
authors.forename: Fang-Chi
authors.initials: FC
authors.lastname: Hsu
authors.forename: Maggie C-Y
authors.initials: MC
authors.lastname: Ng
authors.forename: Carl D
authors.initials: CD
authors.lastname: Langefeld
authors.forename: J Jeffrey
authors.initials: JJ
authors.lastname: Carr
authors.forename: Barry I
authors.initials: BI
authors.lastname: Freedman
authors.forename: Donald W
authors.initials: DW
authors.lastname: Bowden
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000235:genetics / Q000401:mortality*; D008076:Cholesterol, HDL / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000150:complications / Q000235:genetics* / Q000401:mortality; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D058226:Plaque, Atherosclerotic / Q000150:complications / Q000235:genetics* / Q000401:mortality; D020641:Polymorphism, Single Nucleotide; D061205:Vascular Calcification / Q000150:complications / Q000235:genetics* / Q000401:mortality
chemical_list: D008076:Cholesterol, HDL